Emerson Charlene H, Bertuch Alison A
a Graduate Program in Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
b Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Biochem Cell Biol. 2016 Oct;94(5):396-406. doi: 10.1139/bcb-2016-0001. Epub 2016 Mar 31.
DNA double strand breaks (DSBs) are dangerous sources of genome instability and must be repaired by the cell. Nonhomologous end-joining (NHEJ) is an evolutionarily conserved pathway to repair DSBs by direct ligation of the ends, with no requirement for a homologous template. While NHEJ is the primary DSB repair pathway in mammalian cells, conservation of the core NHEJ factors throughout eukaryotes makes the pathway attractive for study in model organisms. The budding yeast, Saccharomyces cerevisiae, has been used extensively to develop a functional picture of NHEJ. In this review, we will discuss the current understanding of NHEJ in S. cerevisiae. Topics include canonical end-joining, alternative end-joining, and pathway regulation. Particular attention will be paid to the NHEJ mechanism involving core factors, including Yku70/80, Dnl4, Lif1, and Nej1, as well as the various factors implicated in the processing of the broken ends. The relevance of chromatin dynamics to NHEJ will also be discussed. This review illustrates the use of S. cerevisiae as a powerful system to understand the principles of NHEJ, as well as in pioneering the direction of the field.
DNA双链断裂(DSB)是基因组不稳定的危险因素,细胞必须对其进行修复。非同源末端连接(NHEJ)是一种进化上保守的途径,通过直接连接末端来修复DSB,无需同源模板。虽然NHEJ是哺乳动物细胞中主要的DSB修复途径,但核心NHEJ因子在整个真核生物中的保守性使得该途径在模式生物研究中具有吸引力。芽殖酵母酿酒酵母已被广泛用于构建NHEJ的功能图谱。在这篇综述中,我们将讨论目前对酿酒酵母中NHEJ的理解。主题包括经典末端连接、替代末端连接和途径调控。将特别关注涉及核心因子的NHEJ机制,包括Yku70/80、Dnl4、Lif1和Nej1,以及参与断裂末端加工的各种因子。还将讨论染色质动力学与NHEJ的相关性。这篇综述说明了酿酒酵母作为一个强大的系统在理解NHEJ原理以及开拓该领域方向方面的应用。